The Effects of Platycodin D, a Saponin Purified from Platycodi Radix, on Collagen-Induced DBA/1J Mouse Rheumatoid Arthritis

Hindawi Publishing Corporation Evidence-Based Complementary and Alternative Medicine Volume 2014, Article ID 954508, 16 pages http://dx.doi.org/10.1155/2014/954508 Research Article The Effects of Platycodin D, a Saponin Purified from Platycodi Radix, on Collagen-Induced DBA/1J Mouse Rheumatoid Arthritis O. Gon Kwon,1 Sae Kwang Ku,2,3 Hee Duk An,1 and Young Joon Lee2,4 1 Department of Rehabilitation Medicine, College of Korean Medicine, Daegu Haany University, 1 Hannydaero, Gyeongsan, Gyeongsangbuk-Do 712-715, Republic of Korea 2 The Medical Research Center for Globalization of Herbal Medicine, College of Korean Medicine, Daegu Haany University, 1 Hannydaero, Gyeongsan, Gyeongsangbuk-Do 712-715, Republic of Korea 3 Department of Histology and Anatomy, College of Korean Medicine, Daegu Haany University, 1 Hannydaero, Gyeongsan, Gyeongsangbuk-Do 712-715, Republic of Korea 4 Department of Preventive Medicine, College of Korean Medicine, Daegu Haany University, 1 Hannydaero, Gyeongsan, Gyeongsangbuk-Do 712-715, Republic of Korea Correspondence should be addressed to Hee Duk An; and Young Joon Lee; Received 17 August 2013; Accepted 17 December 2013; Published 6 January 2014 Academic Editor: Vincenzo De Feo Copyright © 2014 O. Gon Kwon et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The object of this study is to observe the effects of platycodin D, a saponin purified from Platycodi Radix, on mice collageninduced arthritis (CIA). A daily dose of 200, 100, and 50 mg/kg platycodin D was administered orally to male DBA/1J mice for 40 days after initial collagen immunization. To ascertain the effects administering the collagen booster, CIA-related features (including body weight, poly-arthritis, knee and paw thickness, and paw weight increase) was measured from histopathological changes in the spleen, left popliteal lymph node, third digit, and the knee joint regions. CIA-related bone and cartilage damage improved significantly in the platycodin D-administered CIA mice. Additionally, myeloperoxidase (MPO) levels in the paw were reduced in platycodin D-treated CIA mice compared to CIA control groups. The level of malondialdehyde (MDA), an indicator of oxidative stress, decreased in a dose-dependent manner in the platycodin D group. Finally, the production of IL-6 and TNF𝛼, involved in rheumatoid arthritis pathogenesis, was suppressed by treatment with platycodin D. Taken together, these results suggest that platycodin D is a promising new effective antirheumatoid arthritis agent, exerting anti-inflammatory, antioxidative and immunomodulatory effects in CIA mice. 1. Introduction Rheumatoid arthritis (RA) is a common human autoimmune disease characterized by chronic inflammation of the synovial membranes with concomitant destruction of cartilage and bone. Although the etiology and pathogenesis of RA are not yet understood, it has been suggested that abnormalities of cytokines, such as interleukin (IL)-1, IL-6, and TNF-𝛼, play an important role in the pathogenesis [1]. In addition, the current view of the cytokine network in rheumatoid joints supports the notion that TNF-𝛼 activates a cytokine cascade characterized by the simultaneous production of proinflammatory cytokines such as IL-1 and IL-6 and of anti-inflammatory cytokines such as IL-10, IL-1Ra, and soluble TNF receptor [2]. In epidemiological studies, oxidative damage to proteins, lipids, DNA, cartilage, and extracellular collagen has been demonstrated in patients with RA [3] and moreover has demonstrated an inverse correlation between the dietary intake of antioxidants and the incidence of RA [4]. Lipid peroxidation markers such as serum malondialdehyde (MDA) and urine isoprostane are reported to be elevated in collagen-induced arthritis (CIA) compared with those in controls [5, 6]. As above concepts for pathogenesis of RA, clinical application with TNF-𝛼-neutralizing antibody and IL-1 receptor antagonist exhibits substantial efficacy but carries the disadvantages of high cost, hypersensitivity to 2 Evidence-Based Complementary and Alternative Medicine medications, and possibility of serious infections [7, 8]. In addition, antioxidants also showed favorable effects on the RA but their effects are much lower than the expectation [9, 10]. Therefore, further efforts are necessary to develop new drugs with fewer side effects and much more potent for treatment of RA. As increase of the concern in the functional food and wellbeing in life, the demands and consumption of functional food originated from natural sources are increased [12]. Platycodi Radix, the roots of Platycodon grandiflorum (Jacq.), has been used traditionally as an expectorant and a remedy for bronchitis, tonsillitis, laryngitis, and suppurative dermatitis in China, Korea, and Japan. In China and Korea, the fresh roots of P. grandiflorum have been eaten as pickles for preventing obesity [13]. Platycodin D is a major pharmacological constituent of Platycodi Radix [14], and it has been showen the antidiabetic [14–16], anti-inflammatory [17–19], anticancer [20, 21], antinociceptive [22, 23], and immunomodulatory [24, 25] activities. The object of this study was, therefore, to evaluate the efficacy of platycodin D, a saponin purified from Platycodi Radix on mice CIA. In the present study, 50, 100, and 200 mg/kg of platycodin D were orally administered to male DBA/1J mice for 40 days, once a day from the initial collagen immunization. The changes on the body weight, clinical scores, thicknesses of left knee and paw, spleen, left popliteal lymph node and left hid paw weights, paw myeloperoxidase (MPO; for neutrophil infiltration) and malondialdehyde (MDA; for oxidative stress) contents, paw TNF-𝛼 and interleukin (IL)-6 levels, splenocytes TNF-𝛼 and IL-6 productions and histopathology of spleen, left popliteal lymph node, third digits, and knee joint regions were monitored using established methods. Nonimmunized and nonboosted mice were used as a normal control, and Enbrel, TNF-𝛼 neutralizing antibody, was used as reference substances in this study. were further purified by repeated silica gel (Merck, Germany) chromatography to obtain the purified platycodin D. The process was repeated several times until a sufficient quantity of platycodin D was obtained. The purified platycodin D was identified on the basis of Rf, FAB-MS (=1225.38), and [13 C]-NMR spectra compared with the authentic platycodin D (Figure 1). Prepared platycodin D is light yellow powder and is stored in a desiccator to be protected from light and humidity. Platycodin D is well dissolved (clear light yellow solution) at least 40 mg/mL concentrations in distilled water. Enbrel (Wyeth Korea, Korea) 25 mg/0.5 mL vehicle packed in syringe was purchase from local supplier. In this study, we selected 200 mg/kg of platycodin D as (...truncated)